Insulin-like growth factors (IGFs) are members of the highly diverse insulin gene family that includes insulin, IGF-I, IGF-II, relaxin, prothoraciotropic hormone (PTTH), and molluscan insulin-related peptide (Blundell, T. L. and Humbel, R. E., Nature 287:781-787 (1980); Ebberink, R. H. M. et al., Biol. Bull 177:176-182 (1989); Smit, A. B. et al., Nature 331:535-538 (1989)). IGFs comprise, from amino to carboxy termini, a prepeptide leader followed by a B domain, a C domain, an A domain, a D domain and a carboxy-terminal E domain. The IGFs are circulating, mitogenic peptide hormones that have an important role in stimulating growth, differentiation, metabolism and regeneration both in vitro and in vivo (Froesh, E. R., in Insulin-like Growth Factors/Somatomediams, de Gruyter, S. M. (ed.), New York, pp. 18-29 (1983); Lowe, M. W. Jr., in Insulin-like Growth Factors:Molecular and Cellular Aspects, LeRoith, D. (ed.), Boca Raton, Fla., CRC Press, pp. 49-80 (1991)). IGF-I and IGF-II are produced as prepropeptides; upon post-translation processing, the prepeptide leader sequence and the E domain peptide are cleaved from the prepropeptide to form the mature, bioactive molecule. In trout, four distinct forms of IGF-I mRNA exist (IGF Ea-1, Ea-2, Ea-3 and Ea-4), differing in the lengths of the E domain peptides (Shamblott, M. J. and Chen, T. T., Mol. Mar. Biol. Biotechnol. 2(6):351-361 (1993)). These four mRNA forms have different temporal expression patterns (Greene, M. W. and Chen, T. T., Mol. Mar. Biol. Biotechnol. 6(2):144-151 (1997)).
As described herein, the E domain peptides of rainbow trout insulin-like growth factor I (rtIGF-I) have several biological activities, including mitogenic activity, cell attachment activity, and induction of morphological changes in malignant or oncogenically-transformed cells. The present invention thus pertains to use of an E domain peptide agent, such as an E domain peptide of a trout, an E domain peptide homolog, an E domain peptide fusion protein, or a nucleic acid encoding an E domain peptide, E domain peptide homolog, or E domain peptide fusion protein. In one embodiment, the invention is drawn to methods of increasing mitosis in cells, by administering to the cells at least one E domain peptide agent, particularly Ea-2 domain peptide, Ea-3 domain peptide or Ea-4 domain peptide. In another embodiment, the invention is drawn to methods of increasing cell attachment in culture (e.g., cell culture or tissue culture), by providing to the cells an E domain peptide agent, particularly Ea-2 domain peptide and/or Ea-4 domain peptide, in the cell culture medium. The invention also provides a culture medium containing one or more E domain peptide agents (e.g., to supplement or replace fetal bovine serum). In yet another embodiment, the invention is drawn to methods of enhancing wound healing, by administering to the wound one or more E domain peptide agents. In a further embodiment, the invention is drawn to methods of inhibiting proliferation of malignant cells, either in vitro or in vivo, by administering one or more E domain peptide agents to the malignant cells.